tbuckley/cabot-search huggingface dataset:
Medicaid Expansion of the Patient Protection and Affordable Care Act and Participation of Patients With Medicaid in Cancer Clinical Trials
Authors: Joseph M. Unger, Hong Xiao, Riha Vaidya, Michael LeBlanc, Dawn L. Hershman
Journal: JAMA Oncology (2023)

Importance The Patient Protection and Affordable Care Act (ACA) Medicaid expansion resulted in increased use of Medicaid insurance nationwide. However, the association between Medicaid expansion and access to clinical trials has not been examined to date. Objective To examine whether the implementation of ACA Medicaid expansion was associated with increased participation of patients with Medicaid insurance in cancer clinical trials. Design, Setting, and Participants Data for this cohort study of 51 751 patients were from the SWOG Cancer Research Network. All patients aged 18 to 64 years and enrolled in treatment trials with Medicaid or private insurance between April 1, 1992, and February 29, 2020, were included. Interrupted time-series analysis with segmented logistic regression was used. The monthly unemployment rate and presidential administration were adjusted to reflect potential differences in Medicaid use associated with economic conditions and national administrative policies, respectively. Data analysis was conducted between June 22, 2021, and August 5, 2022. Exposure Implementation of Medicaid expansion on January 1, 2014, was the independent exposure variable. Main Outcomes and Measures The number and proportion of patients by insurance type enrolled in cancer clinical trials over time were analyzed. Results Overall, data for 51 751 patients were analyzed. Mean (SD) age was 50.6 (9.8) years, 67.3% of patients were female, 41.1% were younger than 50 years, and 9.1% used Medicaid. A 19% annual increase (odds ratio [OR], 1.19; 95% CI, 1.11-1.28; P &amp;amp;lt; .001) was identified in the odds of patients using Medicaid after the ACA Medicaid expansion, resulting in a 52% increase (OR, 1.52; 95% CI, 1.29-1.78; P &amp;amp;lt; .001) compared with what was expected in the number of Medicaid patients enrolled over time. The association was greater in states that adopted Medicaid expansion in 2014 to 2015 (OR, 1.26; 95% CI, 1.15-1.38; P &amp;amp;lt; .001) compared with other states (OR, 1.08; 95% CI, 0.96-1.21; P = .20; P = .04 for interaction). By February 2020, the proportion of patients with Medicaid insurance was 17.8% (95% CI, 15.0%-20.8%; P &amp;amp;lt; .001), whereas the expected proportion had ACA Medicaid expansion not occurred was 6.9% (95% CI, 4.4%-10.3%; P &amp;amp;lt; .001). Conclusions and Relevance Findings suggest that implementation of ACA Medicaid expansion was associated with increased participation of patients using Medicaid in cancer clinical trials. Improved participation in clinical trials for Medicaid-insured patients is critical for socioeconomically vulnerable patients seeking access to the newest treatments available in trials and for improving confidence that trial findings apply to patients of all backgrounds.
Remdesivir: A Review in COVID-19
Authors: Hannah A. Blair
Journal: Drugs (2023)

Remdesivir (Veklury®), a nucleotide analogue prodrug with broad-spectrum antiviral activity, is approved for the treatment of coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 infection. Unlike some antivirals, remdesivir has a low potential for drug-drug interactions. In the pivotal ACTT-1 trial in hospitalized patients with COVID-19, daily intravenous infusions of remdesivir significantly reduced time to recovery relative to placebo. Subsequent trials provided additional support for the efficacy of remdesivir in hospitalized patients with moderate or severe COVID-19, with a greater benefit seen in patients with minimal oxygen requirements at baseline. Clinical trials also demonstrated the efficacy of remdesivir in other patient populations, including outpatients at high risk for progression to severe COVID-19, as well as hospitalized paediatric patients. In terms of mortality, results were equivocal. However, remdesivir appeared to have a small mortality benefit in hospitalized patients who were not already being ventilated at baseline. Remdesivir was generally well tolerated in clinical trials, but pharmacovigilance data found an increased risk of hepatic, renal and cardiovascular adverse drug reactions in the real-world setting. In conclusion, remdesivir represents a useful treatment option for patients with COVID-19, particularly those who require supplemental oxygen. Coronavirus disease 2019 (COVID-19) was first reported in China in 2019 and quickly spread around the world. The symptoms of COVID-19 can vary from person to person, with some people having no symptoms and others becoming very unwell. Most patients with COVID-19 can treat their symptoms at home, but some patients may be admitted to hospital and/or treated with specialized medications such as remdesivir (Veklury®). Remdesivir is an antiviral medicine that can reduce the amount of virus that causes COVID-19. It is given once a day, usually for 5–10 days, as an intravenous infusion. Remdesivir has been shown to improve the recovery time in hospitalized patients with COVID-19, including children and adolescents. It may also reduce the risk of death in hospitalized patients who are not being ventilated before they start treatment. A 3-day course of remdesivir is also effective in patients whose age or underlying health puts them at high risk for becoming severely ill. The drug is generally well tolerated. Therefore, remdesivir is a useful treatment option for patients with COVID-19, especially those who require additional oxygen.
Targeted delivery of CD163+ macrophage-derived small extracellular vesicles via RGD peptides promote vascular regeneration and stabilization after spinal cord injury
Authors: Wei Peng, Yong Xie, Yudong Liu, Jiaqi Xu, Feifei Yuan, Chengjun Li, Tian Qin, Hongbin Lu, Chunyue Duan, Jianzhong Hu
Journal: Journal of Controlled Release (2023)
The gut microbiome contributes to somatic morphine withdrawal behavior and implicates a TLR2 mediated mechanism
Authors: Bridget Truitt, Greeshma Venigalla, Praveen Singh, Salma Singh, Junyi Tao, Irina Chupikova, Sabita Roy
Journal: Gut Microbes (2023)

The ongoing opioid epidemic has left millions of people suffering from opioid use disorder due to the over-prescription of highly addictive substances. Chronic opioid exposure leads to dependence, where the absence of the drug results in negative symptoms of withdrawal, often driving patients to continue drug use; however, few therapeutic strategies are currently available to combat the cycle of addiction and the severity of morphine withdrawal. This study investigates the microbiome as a potential therapeutic target for morphine withdrawal, as gut dysbiosis caused by morphine use has been proven to contribute to other aspects of opioid use disorders, such as tolerance. Results show that although the microbiome during morphine withdrawal trends toward recovery from morphine-induced dysbiosis, there continues to be a disruption in the alpha and beta diversity as well as the abundance of gram-positive bacteria that may still contribute to the severity of morphine withdrawal symptoms. Germ-free mice lacking the microbiome did not develop somatic withdrawal symptoms, indicating that the microbiome is necessary for the development of somatic withdrawal behavior. Notably, only TLR2 but not TLR4 whole-body knockout models display less withdrawal severity, implicating that the microbiome, through a gram-positive, TLR2 mediated mechanism, drives opioid-induced somatic withdrawal behavior.
Anti‐HER2 Super Stealth Immunoliposomes for Targeted‐Chemotherapy
Authors: Elena Canato, Antonella Grigoletto, Ilaria Zanotto, Tommaso Tedeschini, Benedetta Campara, Giovanna Quaglio, Giuseppe Toffoli, Delia Mandracchia, Alberto Dinarello, Natascia Tiso, Francesco Argenton, Katia Sayaf, Maria Guido, Daniela Gabbia, Sara De Martin, Gianfranco Pasut
Journal: Advanced Healthcare Materials (2023)

Abstract Liposomes play an important role in the field of drug delivery by virtue of their biocompatibility and versatility as carriers. Stealth liposomes, obtained by surface decoration with hydrophilic polyethylene glycol (PEG) molecules, represent an important turning point in liposome technology, leading to significant improvements in the pharmacokinetic profile compared to naked liposomes. Nevertheless, the generation of effective targeted liposomes—a central issue for cancer therapy—has faced several difficulties and clinical phase failures. Active targeting remains a challenge for liposomes. In this direction, a new Super Stealth Immunoliposomes (SSIL2) composed of a PEG‐bi‐phospholipids derivative is designed that stabilizes the polymer shielding over the liposomes. Furthermore, its counterpart, conjugated to the fragment antigen‐binding of trastuzumab (Fab’ TRZ ‐PEG‐bi‐phospholipids), is firmly anchored on the liposomes surface and correctly orients outward the targeting moiety. Throughout this study, the performances of SSIL2 are evaluated and compared to classic stealth liposomes and stealth immunoliposomes in vitro in a panel of cell lines and in vivo studies in zebrafish larvae and rodent models. Overall, SSIL2 shows superior in vitro and in vivo outcomes, both in terms of safety and anticancer efficacy, thus representing a step forward in targeted cancer therapy, and valuable for future development.
Immuno‐Nanozymes Mediated Synergistic Chemodynamic/Immuno‐Therapy with Potentiated Anti‐Tumor Efficacy
Authors: Yuying Yin, Hao Wang, Jingqiang Xue, Chenlu Yin, Yixin Xing, Wei Gu
Journal: Advanced Healthcare Materials (2023)

Nanozymes mediated chemodynamic therapy (CDT) is a newly developed therapeutic modality with high specificity. The efficacy of CDT, however, still confronts challenges from the immune inhibitory tumor microenvironment (TME). It is thus of great significance to synergize CDT with immunotherapeutic interventions. Herein, this work reports the design and preparation of CpG loaded, Cu2+ doped double layered hydroxides nanosheets (CpG/Cu-LDHs) as immuno-nanozymes to potentiate overall anti-tumor efficacy by synergizing CDT with immunogenic cell death (ICD)-activated local and systemic immune responses. Such cooperative CDT-immuno effect together with immunosuppressive TME remodeling capacity conferred by CpG/Cu-LDHs led to effective suppression of both treated primary tumor and untreated distant tumor on a mouse tumor model. Thereby, synergizing CDT with ICD-driven, in situ vaccine-like immunotherapy by immuno-nanozymes provides a novel and generalized paradigm for devising highly efficient and specific anti-tumor strategy without the use of external stimulations.
A review of current therapeutics targeting the mitochondrial protease ClpP in diffuse midline glioma, H3 K27-altered
Authors: Evangeline R Jackson, Mika L Persson, Cameron J Fish, Izac J Findlay, Sabine Mueller, Javad Nazarian, Esther Hulleman, Jasper van der Lugt, Ryan J Duchatel, Matthew D Dun
Journal: Neuro-Oncology (2023)

Abstract Diffuse midline gliomas (DMGs) are devastating pediatric brain tumors recognized as the leading cause of cancer-related death in children. DMGs are high-grade gliomas (HGGs) diagnosed along the brain’s midline. Euchromatin is the hallmark feature of DMG, caused by global hypomethylation of H3K27 either through point mutations in histone H3 genes (H3K27M), or by overexpression of the enhancer of zeste homolog inhibitory protein. In a clinical trial for adults with progressive HGGs, a 22-year-old patient with a thalamic DMG, H3 K27-altered, showed a remarkable clinical and radiological response to dordaviprone (ONC201). This response in an H3 K27-altered HGG patient, coupled with the lack of response of patients harboring wildtype-H3 tumors, has increased the clinical interest in dordaviprone for the treatment of DMG. Additional reports of clinical benefit have emerged, but research defining mechanisms of action (MOA) fall behind dordaviprone’s clinical use, with biomarkers of response unresolved. Here, we summarize dordaviprone’s safety, interrogate its preclinical MOA identifying the mitochondrial protease “ClpP” as a biomarker of response, and discuss other ClpP agonists, expanding the arsenal of potential weapons in the fight against DMG. Finally, we discuss combination strategies including ClpP agonists, and their immunomodulatory effects suggestive of a role for the tumor microenvironment in DMG patient response.
<i>L. rhamnosus</i> CNCM I-3690 survival, adaptation, and small bowel microbiome impact in human
Authors: Edoardo Zaccaria, Tim Klaassen, Annick M.E. Alleleyn, Jos Boekhorst, Christian Chervaux, Tamara Smokvina, Freddy J. Troost, Michiel Kleerebezem
Journal: Gut Microbes (2023)

Fermented foods and beverages are a significant source of dietary bacteria that enter the gastrointestinal (GI) tract. However, little is known about how these microbes survive and adapt to the small intestinal environment. Colony-forming units (CFU) enumeration and viability qPCR of Lacticaseibacillus rhamnosus CNCM I-3690 in the ileal effluent of 10 ileostomy subjects during 12-h post consumption of a dairy product fermented with this strain demonstrated the high level of survival of this strain during human small intestine passage. Metatranscriptome analyses revealed the in situ transcriptome of L. rhamnosus in the small intestine, which was contrasted with transcriptome data obtained from in vitro cultivation. These comparative analyses revealed substantial metabolic adaptations of L. rhamnosus during small intestine transit, including adjustments of carbohydrate metabolism, surface-protein expression, and translation machinery. The prominent presence of L. rhamnosus in the effluent samples did not elicit an appreciable effect on the composition of the endogenous small intestine microbiome, but significantly altered the ecosystem's overall activity profile, particularly of pathways associated with carbohydrate metabolism. Strikingly, two of the previously recognized gut-brain metabolic modules expressed in situ by L. rhamnosus (inositol degradation and glutamate synthesis II) are among the most dominantly enriched activities in the ecosystem's activity profile. This study establishes the survival capacity of L. rhamnosus in the human small intestine and highlights its functional adjustment in situ, which we postulate to play a role in the probiotic effects associated with this strain.
Effect of a Nutrition Intervention on Mediterranean Diet Adherence Among Firefighters
Authors: Maria Soledad Hershey, Chia-Rui Chang, Mercedes Sotos-Prieto, Alejandro Fernandez-Montero, Sean B. Cash, Costas A. Christophi, Sara C. Folta, Carolyn Muegge, Vanessa Kleinschmidt, Steven Moffatt, Dariush Mozaffarian, Stefanos N. Kales
Journal: JAMA Network Open (2023)

US firefighters are a working population at risk of chronic diseases, including obesity, cardiovascular disease, and cancer. This risk may be mitigated by a healthy diet.To evaluate the effect of a Mediterranean nutrition intervention using a behavioral/environmental approach (firefighter/fire station/home) at the individual participant level.This 12-month cluster randomized clinical trial included US career firefighters from fire stations and homes within 2 Indiana fire departments. Participants were randomized by fire station to either Mediterranean diet or control (usual care). The study was conducted from October 2016 to December 2019, and data were analyzed in November 2022.For the first 12 months of the study, firefighters located at fire stations randomized to the intervention group were provided with access to supermarket discounts and free samples of Mediterranean diet foods, online nutrition education platforms, email announcements and reminders, family and peer education and support, and chef demonstrations. Firefighters in fire stations allocated to the control group received no intervention and were instructed to follow their usual diet.Change in dietary habits at 12 months as measured by a modified Mediterranean diet score (range, 0 to 51 points) at baseline and 6-month and 12-month follow-up. Cardiometabolic parameters were secondary outcomes.Of 485 included firefighters, 458 (94.4%) were male, and the mean (SD) age was 47 (7.5) years. A total of 241 firefighters (27 fire stations) were randomized to the Mediterranean nutrition intervention, and 244 (25 fire stations) were randomized to usual diet. Outcomes were analyzed using generalized linear mixed models for modified Mediterranean diet score at 6 months (n = 336) and 12 months (n = 260), adjusting for baseline age, sex, race and ethnicity, fire department, physical activity, and waist circumference. In the intervention group compared with the control group, the modified Mediterranean diet score significantly increased by 2.01 points (95% CI, 0.62-3.40; P = .005) at 6 months and by 2.67 points (95% CI, 1.14-4.20; P = .001) at 12 months. Among secondary outcomes, changes in cardiometabolic risk factors were not statistically significant at 1 year. Results from analyses with multilevel multiple imputation for missingness were similar.In this Mediterranean nutrition intervention of multicomponent behavioral/environmental changes, career firefighters had increased adherence to a Mediterranean diet.ClinicalTrials.gov Identifier: NCT02941757.
Medicaid Expansion and Clinical Trials—Why Doing the Right Thing Helps Us Do the Best Science
Authors: Samilia Obeng-Gyasi, Oluwadamilola M. Fayanju
Journal: JAMA Oncology (2023)

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Epidemiology, surveillance and diagnosis of Usutu virus infection in the EU/EEA, 2012 to 2021
Authors: Giorgia Angeloni, Michela Bertola, Elena Lazzaro, Matteo Morini, Giulia Masi, Alessandro Sinigaglia, Marta Trevisan, Céline M. Gossner, Joana M. Haussig, Tamas Bakonyi, Gioia Capelli, Luisa Barzon
Journal: Eurosurveillance (2023)

Background Usutu virus (USUV) is a flavivirus with an enzootic cycle between birds and mosquitoes; humans are incidental dead-end hosts. In Europe, the virus was first detected in Italy in 1996; since then, it has spread to many European countries. Aim We aimed to report on the epidemiology, surveillance, diagnosis and prevention of USUV infection in humans, mosquitoes and other animals in the European Union/European Economic Area (EU/EEA) from 2012 to 2021. Methods We collected information through a literature review, an online survey and an expert meeting. Results Eight countries reported USUV infection in humans (105 cases, including 12* with neurological symptoms), 15 countries in birds and seven in mosquitoes. Infected animals were also found among pets, wild and zoo animals. Usutu virus was detected primarily in Culex pipiens but also in six other mosquito species. Detection of USUV infection in humans is notifiable only in Italy, where it is under surveillance since 2017 and now integrated with surveillance in animals in a One Health approach. Several countries include USUV infection in the differential diagnosis of viral encephalitis and arbovirus infections. Animal USUV infection is not notifiable in any EU/EEA country. Conclusion Human USUV infections, mainly asymptomatic and, less frequently, with a febrile illness or a neuroinvasive disease, have been reported in several EU/EEA countries, where the virus is endemic. Climate and environmental changes are expected to affect the epidemiology of USUV. A One Health approach could improve the monitoring of its evolution in Europe.
A comparison of two registry-based systems for the surveillance of persons hospitalised with COVID-19 in Norway, February 2020 to May 2022
Authors: Robert Whittaker, Salla Toikkanen, Katharine Dean, Trude Marie Lyngstad, Eirik Alnes Buanes, Hilde Kløvstad, Trine Hessevik Paulsen, Elina Seppälä
Journal: Eurosurveillance (2023)

BackgroundThe surveillance of persons hospitalised with COVID-19 has been essential to ensure timely and appropriate public health response. Ideally, surveillance systems should distinguish persons hospitalised with COVID-19 from those hospitalised due to COVID-19.AimWe compared data in two national electronic health registries in Norway to critically appraise and inform the further development of the surveillance of persons hospitalised with COVID-19.MethodWe included hospitalised COVID-19 patients registered in the Norwegian Patient Registry (NPR) or the Norwegian Pandemic Registry (NoPaR) with admission dates between 17 February 2020 and 1 May 2022. We linked patients, identified overlapping hospitalisation periods and described the overlap between the registries. We described the prevalence of International Classification of Diseases (ICD-10) diagnosis codes and their combinations by main cause of admission (clinically assessed as COVID-19 or other), age and time.ResultsIn the study period, 19,486 admissions with laboratory-confirmed COVID-19 were registered in NoPaR and 21,035 with the corresponding ICD-10 code U07.1 in NPR. Up to late 2021, there was a 90-100% overlap between the registries, which thereafter decreased to < 75%. The prevalence of ICD-10 codes varied by reported main cause, age and time.ConclusionChanges in patient cohorts, virus characteristics and the management of COVID-19 patients from late 2021 impacted the registration of patients and coding practices in the registries. Using ICD-10 codes for the surveillance of persons hospitalised due to COVID-19 requires age- and time-specific definitions and ongoing validation to consider temporal changes in patient cohorts and virus characteristics.